Chapter 26: The Urinary System Part 2 Flashcards
3 processes are involved in urine formation and adjustment of blood composition:
- Glomerular Filtration
- Tubular Reabsorption
- Tubular Secretion
Glomerular Filtration
is a passive and nonselective process (no metabolic energy required)
• Hydrostatic pressure forces fluids and solutes through filtration membrane into glomerular capsule
• No reabsorption into capillaries of glomerulus occur
Tubular Reabsorption
selectively returns 99% of substances from filtrate to blood in renal tubules and collecting ducts
Tubular Secretion
- reabsorption in reverse
- primarily occurs in the distal convoluted tubule when active transport moves substances like creatine and penicillin, from the blood into this tubule.
- disposes of unwanted solutes, eliminates solutes that were reabsorbed, rids the body of excess K+, and controls blood pH.
- Tubular secretion is most active in the proximal convoluted tubule, but occurs in the collecting ducts and distal convoluted tubules, as well.
Glomerular Blood Hydrostatic Pressure (GBHP) or Hydrostatic Pressure in Glomerular Capillaries (HPgc)
- It is the pressure of blood in the glomerular capillaries
- Chief force pushing water & solutes out of blood
- Glomerular Blood Pressure: 55 mmHg
Capsular Hydrostatic Pressure (CHP) or Hydrostatic pressure in capsular space (HPcs)
- Opposing force to GBHP by fluid already in the capsular space that tends to push water and solutes out of the filtrate and back into plasma
- results from the resistance to flow along the nephron and conducting system
- Filtrate Pressure in Capsule: 15 mm Hg
Blood Colloid Osmotic Pressure (BCOP) or Colloid osmotic pressure in capillaries (OPgc)
- pressure exerted by the proteins in the plasma which tends to retain fluid and also oppose filtration
- pulls fluid into capillaries from interstitial spaces
- “Pull” of Proteins in Blood: 30 mm Hg
Explain what is meant from NFP
Net Filtration Pressure (NFP): sum of forces
• Pressure responsible for filtrate formation
• Main controllable factor determining Glomerular Filtration Rate (GFR)
How is Net Filtration Pressure calculated?
NFP = GBHP (outward pressures) - (CHP + BCOP) (inward pressures)
= 55 - (15 + 30) -> NFP = 10 mm Hg
What forces determine filtration pressure?
- Glomerular (blood) hydrostatic pressure GHP or GBHP
- Capsular Hydrostatic Pressure (CHP)
- (Blood) Colloid Osmotic Pressure (BCOP)
Glomerular Filtration Rate (GFR) is influenced by
- Net filtration pressure
- Total surface area for filtration
- filtration membrane permeability
What is the relationship between glomerular filtration rate (GFR) and NFP?
- Primary factor that influences GFR (primary pressure is glomerular blood hydrostatic pressure (GBHP)
- Increase NFP = Increase GFR (directly proportional)
How does total surface area for filtration influence the rate of glomerular filtration rate?
Glomerular mesangial cells control by contracting
How does filtration membrane permeability influence glomerular filtration rate?
Much more permeable than other capillaries
How is GFR regulated?
- intrinsic controls (renal autoregulation)
2. extrinsic controls
Why is it important to maintain a constant GFR?
Constant GFR is important as it allows kidneys to make filtrate and maintain extracellular homeostasis
Increased GFR causes
increased urine output, which lowers blood pressure, and vice versa
Intrinsic Controls: Renal Autoregulation of GFR
-Main goal is to maintain GFR in the kidney
-Maintains nearly constant GFR when MAP is in range of 80–180 mm Hg
• Autoregulation stops if out of that range
2 Types of Renal Autoregulation:
- Myogenic Mechanism
2. Tubuloglomerular Feedback Mechanism
Myogenic Mechanism
Local smooth muscle (walls of afferent arteriole) contracts when stretched
– Increased MAP or Decreased MAP
Both help maintain normal GFR despite normal fluctuations in systemic blood pressure (MAP)
What happens when MAP is increased during the myogenic mechanism?
constriction of afferent arterioles:
- Reduces blood flow into glomerulus -> decreases GBHP
- Protects glomeruli from damaging high BP
What happens when MAP is decreased during the myogenic mechanism?
dilation of afferent arterioles:
-Increases blood flow into glomerulus -> increases GBHP
Tubuloglomerular Feedback Mechanism
Flow-dependent mechanism directed by macula densa cells of JGA
- Respond to:
- filtrate’s NaCl concentration (filtrate’s osmolarity) &/or
- flow of filtrate in renal tubules
Extrinsic Controls
– Purpose of extrinsic controls is to regulate GFR to maintain systemic blood pressure
– Extrinsic controls will override renal intrinsic controls if blood volume needs to be increase
What mechanisms do extrinsic controls use?
- Neural Mechanisms
2. Hormonal Mechanisms
Neural Mechanisms
Sympathetic Nervous System
• During Rest:
– Renal blood vessels (including afferent & efferent arterioles): dilate
– Renal autoregulation mechanisms prevail
• During Stress or Emergency: Low BP/blood volume (blood loss; excessive fluid loss – chronic diarrhea, frequent vomiting; dehydration) or High BP (exercise)
– Norepinephrine is released by sympathetic nervous system and epinephrine is released by adrenal
medulla
Release of norepinephrine and epinephrine by neural mechanisms causes
- Systemic vasoconstriction (including renal blood vessels): increases blood pressure, and reduces blood flow to the kidneys
- Strong constriction of afferent arterioles: significantly decreases GFR (decrease in urine output)
- Blood Volume and Blood Pressure: Increase
Hormonal Mechanisms
- Atrial Natriuretic Peptide (ANP)
2. Renin-Angiotensin-Aldosterone System (RAAS)
Atrial Natriuretic Peptide (ANP)
- released by cells of the atria when blood pressure/blood volume increases
- causes relaxation of glomerular mesangial cells -> increases capillary surface area -> increases GFR
Renin-Angiotensin-Aldosterone System (RAAS)
- when blood pressure/blood volume decreases -> main mechanism for increasing blood pressure/blood volum
3 Pathways to Renin release by Juxtaglomerular Cells (Granular Cells):
- Direct stimulation of granular cells by sympathetic nervous system
- Stimulation by activated macula densa cells when filtrate NaCl concentration is low
- Reduced stretch of granular cells
Anuria
abnormally low urinary output (less than 50 ml/day)
• May indicate that glomerular blood pressure is too low to cause filtration
• Renal failure and anuria can also result from situations in which nephrons stop functioning
– Example: acute nephritis, transfusion reactions, and crush injuries
What are the two routes of tubular reabsorption?
- transcellular route
2. paracellular route
Transcellular Route (Transcellular Reabsorption)
- Solute enters apical membrane of tubule cells
- Travels through cytosol of tubule cells
- Exits basolateral membrane of tubule cells
- Enters blood through endothelium of peritubular capillaries
Paracellular Route (Paracellular Reabsorption)
Between tubule cells
– Limited by tight junctions, but leaky in PCT
» Water, Ca2+, Mg2+, K+, and some Na+ in the PCT move via this route
Proximal Convoluted Tubule (PCT)
– Site of most reabsorption:
• All nutrients, such as glucose and amino acids, are 100% reabsorbed
• 65% of Na+, K+ and water reabsorbed
• Many ions (passive diffusion): 50% Cl-, 80% - 90% bicarbonate, variable amounts of calcium and phosphate • 50% of urea
Tubular Reabsorption of Sodium
- transported across apical membrane
2. transported across basolateral membrane
What happens to sodium as it is transported across the apical membrane?
Na+ enters tubule cell at apical surface via secondary active transport (cotransport) or via facilitated diffusion through channels:
- Active pumping of Na+ at basolateral membrane results in strong electrochemical gradient within tubule cell
– Results in low intracellular Na+ levels that facilitates Na+ diffusion
Sodium transported across basolateral membrane
– Na+ is most abundant cation in filtrate
– Transport of Na+ across basolateral membrane of tubule cell is via primary active transport
– Na+-K+ ATPase pumps Na+ into interstitial space
– Na+ is then swept by bulk flow into peritubular capillaries
Transport Maximum
Transcellular transport systems are specific and limited
– Transport maximum (Tm) exists for almost every reabsorbed substance and reflects number of carriers in renal tubules that are available
-When carriers for a solute are saturated, excess is excreted in urine
Reabsorption Rates of Nephron Loop
Reabsorbs: water: 15% bicarbonate ion: 10-20% Na+ & K+: 20-30% Ca2+ & Mg2+: variable amount Cl-: 35%
Reabsorption in the descending limb of the nephron loop
in the descending limb, H2O can leave, solutes cannot
Reabsorption in the ascending limb of the nephron loop
H2O cannot leave, solutes can :
• Thin segment is passive to Na+ movement
• Thick segment has Na+-K+-2Cl– symporters and Na+-H+ antiporters that transport Na+ into cell
– Some Na+ can pass into cell by paracellular route in this area of limb
Distal Convoluted Tubule (DCT) and Collecting Duct Reabsorption
- Initial Part of DCT: reabsorption of:
- Water: 10-15%
- Na+: 5%
- Cl-:5%
- Major site of PTH (parathyroid hormone) stimulates reabsorption of Ca2+
In the last part of DCT & Collecting Duct, reabsorption is regulated by
hormones (ADH, aldosterone, Atrial Natriuretic Peptide (ANP), Parathyroid Hormone (PTH))
Antidiuretic hormone (ADH)
increase water reabsorption
• Released by posterior pituitary gland
• Causes principal cells of collecting ducts and latter part of DCT to insert aquaporins in apical membranes ->
increasing water reabsorption
Aldosterone
- increase blood pressure and decrease K+ levels
- Targets principal cells of collecting ducts
- Promotes synthesis of: apical Na+-Cl-symporter and K+ channels, and basolateral Na+-K+ ATPases for Na+ reabsorption (H2O follows, if it can)
- As a result, little Na+ leaves body
Without aldosterone
daily loss of filtered Na+ would be 2%, which is incompatible with life.
Where is aldosterone produced in the body?
produced in the cortex of the adrenal glands
Atrial Natriuretic Peptide (ANP)
– Reduces Na+ and water reabsorption at PCT and Collecting Ducts –> resulting in decreased blood volume & BP
– Released by cardiac atrial cells if blood volume or blood pressure elevates
Parathyroid Hormone (PTH)
Acts on initial part of DCT to increase Ca2+ reabsorption and inhibits phosphate reabsorption in the PC
ADH Inhibitors
alcohol
Na+ Reabsorption Inhibitors
Caffeine
What is the chemical composition of human urine?
made up of 95% water and 5% solutes:
-nitrogenous wastes: 1. urea (from amino acid breakdown): largest solute component, 2. uric acid (from nucleic acid metabolism), 3. creatine (metabolite of creatine phosphate)
-Other normal solutes found in urine: Na+, K+, PO4
3–, and SO42–, Ca2+, Mg2+ and HCO3
What are the physical characteristics of urine?
- Color and Transparency
- Odor
- pH
- Specific Gravity
Physical Characteristic of Urine: Color and Transparency
• Clear: Cloudy may indicate urinary tract infection
• Pale to deep yellow from urobilin
-Pigment from hemoglobin breakdown: Yellow color deepens with increased concentration
• Abnormal color (pink, brown, smoky): Can be caused by certain foods, bile pigments, blood, drug
Physical Characteristic of Urine: Odor
- Slightly aromatic when fresh
- Develops ammonia odor upon standing as bacteria metabolize urea
- May be altered by some drugs or vegetables
- Disease may alter smell: ex) Patients with diabetes may have acetone smell to urine
Physical Characteristic of Urine: pH
- Urine is slightly acidic (~pH 6, with range of 4.5 to 8.0)
- Acidic diet (protein, whole wheat) can cause drop in pH • Alkaline diet (vegetarian), prolonged vomiting, or urinary tract infections can cause an increase in pH
Physical Characteristic of Urine: Specific Gravity
- Ratio of mass of substance to mass of equal volume of water (specific gravity of water = 1)
- Ranges from 1.001 to 1.035 because urine is made up of water and solute
Diuretics
Chemicals that enhance urinary output by decreasing water reabsorption:
- ADH inhibitors
- Na+ Reabsorption Inhibitors
- Loop Diuretics
- Osmotic Diuretics
Loop Diuretics
inhibit Na+-K+-2Cl- symporters (thick ascending limb of nephron loop) - inhibit medullary gradient
formation
Osmotic Diuretics
substance not reabsorbed, so water remains in urine
Chronic renal disease
defined as a GFR
Renal failure
defined as GFR
hemodialysis
- a machine filters wastes, salts and fluid from your blood when your kidneys are no longer healthy enough to do this work adequately
- is the most common way to treat advanced kidney failure.
incontinence
the loss of bladder control
hypernatremia
- excess of the electrolyte Sodium (Na+)
- may occur with dehydration, water deprivation or excessive sodium in diet or intravenous fluids
- causes hypertonicity of ECF which pulls water out of body cells into ECF, causing cellular dehydration
Signs and Symptoms of hypernatremia
intense thirst, hypertension, edema, agitation and convulsions
hyponatremia
- deficiency of the electrolyte Sodium (Na+)
- may be due to:
- decreased sodium intake
- increased sodium loss through vomiting, diarrhea or taking certain diuretics
- excessive water intake
hypokalemia
- excess of electrolyte potassium (K+)
- may be due to excessive pottasium intake, renal failur, aldosterone deficiency, crushing injuries to body tissues or transfusion of hemolyzed blood.
hypokalemia
- deficiency of electrolyte potassium (K+)
- may result from excessive loss due to vomiting diarrhea, decreased potassium intake, hyperaldosteronism, kidney disease, and therapy with some diuretics
hypocalcemia
- deficiency of electrolyte calcium (Ca2+)
- may be due to increased calcium loss, reduced calcium intake, elevated phosphate levels or hypoparathyroidism
hypercalcemia
- excess of electrolyte calcium (Ca2+)
- may result from hyperparathyroidism, some cancers, excessive intake of vitamin D, and Paget’s disease of bone
Physiology of the Kidney
~ 180 L (47 gallons) of blood-derived fluid processed daily, but only 1 - 2 L of urine is formed
• Kidneys filter body’s entire plasma volume 60 times each day
• Consume 20–25% of oxygen used by body at rest
• Filtrate (produced by glomerular filtration): blood plasma minus large to medium-sized proteins & blood cells
Urine
• Urine is produced from filtrate
•
Outward Pressures
forces that promote filtrate formation
includes glomerular blood hydrostatic pressure (GBHP) or Hydrostatic pressure in glomerular capillaries (HPgc)
Inward Pressures
- forces inhibiting filtrate formation
- includes capuslar hydrostatic pressure (CHP) and blood colloid osmotic pressure (BCOP)
Where does tubular secretion occur?
occurs almost completely in PCT, but also in cortical parts of collecting ducts and late regions of the DCT
Tubular secretion is important for:
- Disposing of substances, such as drugs or metabolites, that are bound to plasma proteins
- Eliminating undesirable substances that were passively reabsorbed (example: urea and uric acid)
- Ridding body of excess K+ (aldosterone effect)
- Controlling blood pH by altering amounts of H+ or HCO3
– in urine
Filtration Membrane
Porous membrane between blood and interior of glomerular capsule
– Allows water and solutes smaller than plasma proteins to pass (Normally no cells can pass)
What are the three layers of the filtration membrane?
- Fenestrated Endothelium of glomerular capillaries (Pore)
- Basal Lamina of Glomerulus
- Slit Membrane: Foot Processes of Podocytes (Pedicel) with filtration slits
Function of the fenstrated endothelium of glomerular capillaries
prevents filtration of blood cells but allows all components of blood plasma to pass through
Function of the basal lamina of glomerulus
prevents filtration of larger proteins
Function of slit membrane between pedicels
prevents filtration of medium-sized proteins
What provides energy and means for reabsorbing almost every other substances (nutrients, water, ions)?
Na+ reabsorption by primary active transport
Secondary Active Transport
– Electrochemical gradient created by pumps at basolateral surface give “push” needed for transport of other solutes
– Organic nutrients reabsorbed by secondary active transport are cotransported with Na+ via Na+-symporters
• Glucose, amino acids, some ions, vitamin
Passive Tubular Reabsorption of Water
– Movement of Na+ and other solutes creates osmotic gradient for water
– Water is reabsorbed by osmosis, aided by water-filled pores called aquaporins: obligatory and facultative water reabsorption
Obligatory water reabsorption
– Aquaporins are always present in PCT and Descending Limb of Nephron Loops
Facultative water reabsorption
– Aquaporins are inserted in collecting ducts only if ADH is present
Passive Tubular Reabsorption of Solutes
- Solute concentration in filtrate increases as water is reabsorbed (Creates concentration gradients for solutes, which drive their entry into tubule cell and peritubular capillaries)
– Fat-soluble substances, some ions, and urea will follow water into peritubular capillaries down their concentration gradients
Urea helps form medullary gradient:
- Urea enters filtrate in ascending thin limb of nephron loop by facilitated diffusion
- Cortical collecting duct reabsorbs water, leaving urea behind
- In deep medullary region, now highly concentrated urea leaves collecting duct and enters interstitial fluid of medulla
• Urea then moves back into ascending thin limb
• Contributes to high osmolality in medulla
glycosuria
glucose in urine
possible causes is diabetes mellitus
proteinuria or albuminuria
proteins in urine
causes: non pathological:excessive physical exertion, pregnancy
pathaological: glomerulonephritis, severe hypertension, heart failure, often sign of renal disease
ketonuria
ketone bodies in urine
causes: excessive formation and accumulation of ketone bodies, as in starvation and untreated diabetes melitus
hemoglobinuria
hemoglobin in urine
causes: various: transfusion reaction, hemolytic anemia, severe burns
bilirubinuria
bile pigments in urine
causes: liver disease or obstruction of bile ducts from liver or gallbladder
hematuria
erythrocytes in urine
causes: bleeding urinary tract
pyuria
leukocytes in urine
causes: urinary tract infection
